Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are hematologic neoplasms characterized by leukocytosis and hypercellular bone marrow comprised predominantly of granulocytic cells, absence of the Philadelphia chromosome (t(9;22); BCR-ABL1), and absence of platelet-derived growth factor receptor A/B (PDGFRA/B) or fibroblast growth factor receptor 1 (FGFR1) gene rearrangements. CNL is diagnosed based on expansion of neutrophils in both the blood and bone marrow (segmented neutrophils and band forms >80% of white blood cells (WBC)) and is classified as a myeloproliferative neoplasm (MPN) according to World Health Organization (WHO) diagnostic criteria. Cases of aCML exhibit granulocytic dysplasia and increased numbers of neutrophil precursors in both the peripheral blood and the bone marrow (typically ≧10% of WBCs) and are therefore classified as one subtype of the WHO category of myelodysplastic/myeloproliferative neoplasms (Bain, et al., “Chronic neutrophilic leukaemia,” in: Swerdlow, et al., eds. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues (ed 4th). Lyon: IARC Press; 2008:38-39; Vardiman, et al. “Atypical chronic myeloid leukaemia, BCR-ABL1 negative,” in: Swerdlow, et al., WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues (ed 4th). Lyon: IARC Press; 2008:80-81). Occasional cases of CNL (Froberg, et al., Leukemia. 1998; 12:623-626; Matano, et al., Am J Hematol. 1997; 54:72-75) and a majority of aCML cases are reported to exhibit non-specific cytogenetic abnormalities (Hernandez, et al., Ann Oncol. 2000; 11:441-444) or infrequently the JAK2 V617F mutation (Baxter, et al., Lancet. 2005; 365:1054-1061; Steensma, et al., Blood. 2005; 106:1207-1209), revealing the clonal nature of these diseases. The estimated median overall survival is 23.5 months (Elliott, et al., Leukemia. 2005; 19:313-317).
Accordingly, there is a need to develop new methods of treating CNL and aCML in patients. This application is directed to this need and others.